In 1970 5% of licensed pharmaceuticals contained at least one fluorine atom. In 2005 this figure had risen dramatically to 20% and it is now estimated that 25% of current pipeline drugs now contain at least one fluorine atom. The importance of fluorine to pharmaceutical discovery and functionality cannot be overstated. However, industrial methods of chemical fluorination represent some of the most hazardous and toxic chemical methods currently practiced, generally utilizing NaNO2, HF and direct fluorination with F2. Nature, in contrast carries out fluorination with the typically high selectivity of enzymatic reactions and in a mild aqueous environment. The application of "fluorinase" biocatalysts as a complementary approach to chemical synthesis offers the potential of safer, more environmentally acceptable routes to prepare important fluorinated compounds of biomedical importance. We propose to apply a novel high-throughput screening approach to identify and improve new fluorinase biocatalysts from microbial sources. As the initial target we will focus upon a fluorinase, recently identified in Streptomyces cattleya which has been shown to carry out C-F bond formation but which currently possesses activity too low to be industrially useful. We will demonstrate the improvement of this enzyme by directed evolution and the identification of further novel fluorinases from genomic libraries as the proof-of-principle of molecular biological approaches to provide useful biocatalysts which can be developed for industrial fluorination. The fluorinase will be applied also as a synthetic tool for the incorporation of the F-18 isotope into appropriate bio- molecules, particularly in light of the rapid growth in positron emission tomography (PET) as a diagnostic technique and as a requirement for the assessment of the biodistribution of all drugs progressing through clinical trials. [unreadable] [unreadable] The recently discovered microbial fluorinase enzyme converts inorganic fluoride ion to organic fluorine. Biocatalytic incorporation of fluorine opens up a tremendous biotechnological opportunity for clean and safe organofluorine biosynthesis and also the incorporation of radio-labeled fluorine [F-18 isotope] into drugs. The widespread interest in the fluorinase's applicability arises from the huge commercial interest in the fine chemicals, medicinal and agrochemical entities that contain fluorine atoms and also in the growing application of the F-18 isotope in positron emission tomography (PET) applications for medical imaging. The research directed towards improving the efficiency and utility of this fluorination enzyme is unique and numerous applications would follow. [unreadable] [unreadable] [unreadable]